Meropenem is a broad spectrum, beta-lactamase-resistant, carbapenem antibiotic for parenteral administration. The compound of the formula (I) is generically known as meropenem and is used as antibiotic agent in the treatment of pneumonia, urinary tract infections, intra-abdominal, gynaecological, skin, and soft tissue infections, meningitis, septicemia and febrile neutropenia. In USA it is sold under the trade name of MERREM® I.V. (meropenem for injection). MERREM is a sterile, pyrogen-free, synthetic, broad spectrum, carbapenem antibiotic for intravenous administration, and chemically known as (4R,5S,6S)-3-[[(3S,5S)-5-(dimethylcarbamoyl)-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid trihydrate. In view of the importance of the compound of the formula (I), several synthetic procedures to prepare the compound have been reported.
U.S. Pat. No. 4,888,344 provides crystalline Meropenem trihydrate along with non-toxic carbonate composition. According to this patent, Meropenem was obtained by deprotecting the protecting groups of the penultimate compound by hydrogenation as per the following scheme.

U.S. Pat. No. 4,943,569 claims Meropenem and process for its preparation. This patent utilizes buffer like morpholinoalkyl sulfonic acid (MOPS) or its salt during deprotection stage. The description also discloses that the penultimate intermediate (diprotected Meropenem) of Meropenem can be isolated by organochemical means.
According to the above said patents, Meropenem trihydrate was obtained by subjecting the aqueous reaction mass obtained after the deprotection of protecting group, to reverse osmosis (if required), followed by adding water-miscible organic solvent such as ethanol, iso-propanol, acetone, tetrahydrofuran (THF), dioxane, acetonitrile, etc.
IN 198820 provide a method for the preparation of Meropenem wherein biphasic solvent system such as Water-THF-Ethyl acetate was utilized for deprotection (where R′ is allyloxycarbonyl). After deprotection of the protecting groups, the aqueous layer was subjected to crystallization of meropenem trihydrate by the addition of THF.
WO2006/035300 A2 describes a process for preparing Meropenem. This patent publication describes the use of biphasic solvent system for the deprotection step resulting in Meropenem, which is similar to the teachings given in U.S. Pat. No. 4,943,569, where ethyl acetate was added after the hydrogenation to remove organic impurity, and obvious over our Indian patent, 198820. Even though U.S. Pat. No. 4,943,569 teaches the isolation of penultimate, which is not necessary as mentioned, “After completion of the reaction, the reaction product (i.e formula (V)) can be isolated by usual organochemical means”; WO2006/035300A2 publication claims a process for preparing Meropenem trihydrate in which the penultimate compound of formula (V) was not isolated. Similarly, U.S. Pat. No. 4,888,344, which teaches “when the catalytic hydrogenation is carried out in a water-containing organic solvent, the filtrate obtained by filtration of the reaction mixture for removal of the catalyst may be subjected to distillation for evaporation of the organic solvent. In such case, Compound A (Meropenem trihydrate) can be crystallized out directly from the resultant aqueous concentrate. Thus, crystalline Compound A is obtainable without separation and isolation of non-crystalline Compound A, for instance, by column chromatography or lyophilization”, claims a direct process for preparing Meropenem trihydrate in which the crystallization is done directly after deprotection.
WO2005/118586 A1 claims crystalline penultimate compound of formula (V) and a process for preparing this intermediate. According to this publication this intermediate is crystallized out either from concentrating the mother liquor in alkyl alkanoate such as ethyl acetate or by the addition of anti-solvent such as cyclohexane or heptane to the mother liquor in ethyl acetate. Since this patent describes the use of multiple solvent systems, the processes are not commercially viable from industrial point of view owing to multiple solvent recoveries, adding further the cost of production.
As per U.S. Pat. No. 4,888,344 in example 1, Meropenem is dissolved in water, where upon small amount of meropenem crystals formed and further addition of acetone yielded meropenem trihydrate. Since the sterile preparation requires complete dissolution for sterile filtration, this technique is not found attractive.
With our continued research for developing a process for the preparation of compound of formula (I) as sterile product, we have come up with a process, which is not only commercially viable, but also involves simple techniques such as crystallizations, isolation of the penultimate of formula (V) avoiding multiple solvents. None of the prior art suggests or teaches the techniques of the present invention.